1. Field of the Invention
The invention relates to the preparation of ring-opening products of low molecular weight polyglycidyl compounds wherein at least one of the glycidyl epoxide rings remains intact. In particular, the invention relates to a method for the selective ring opening of polyfunctional N-glycidyl compounds by reaction with a hydrohalic acid, a pseudohydrohalic acid, an acid of phosphorus, or an alkali metal salt of these acids, to provide a ring-opening product retaining a predictable number of glycidyl groups in high yield.
The invention further relates to selected ring-opening products, especially N,N'-diglycidyl-N"-(halohydroxypropyl)-urazoles with iodine or fluorine as the halogen substituent, and N-glycidyl-N',N"-bis-(halohydroxypropyl)-urazoles with fluorine, chlorine, bromine or iodine as the halogen substitutent. The new compounds have utility as antitumor agents in mammals, and the invention accordingly includes pharmaceutical compositions comprising compounds of the invention, and methods for inhibiting tumor growth by administering the compounds to a host mammal.
2. Description of the Prior Art
It is known that polyfunctional glycidyl compounds such as heterocycles containing three or more N-glycidyl groups are reactable with proton acids so that a product wherein only one of the epoxide rings of the glycidyl groups is opened, is obtained. In an exemplary process, described in German patent application No. 30 37 094, a polyfunctional N-glycidyl compound is treated with an excess of acid and the reaction terminated prior to completion. While the reaction product includes the monoaddition product, it is a random mixture comprising the starting compound and compounds wherein one, two, or more glycidyl groups are ring-opened. Pure products containing a specific number of intact glycidyl groups of the type required for pharmaceutical use can only be obtained from these mixtures by arduous separation procedures such as column chromatography or high pressure liquid chromatography. Additionally, the strong acids used in such known processes tend to polymerize the glycidyl compounds. Accordingly, there is an unfulfilled need for a selective ring-opening process which permits one or more of the epoxide rings of polyfunctional N-glycidyl compounds to be predictably opened to provide desired mono-, di-, or polyaddition products in high yield.